Systematic biological prioritization after a genome-wide association study: an application to nicotine dependence

Bioinformatics. 2008 Aug 15;24(16):1805-11. doi: 10.1093/bioinformatics/btn315. Epub 2008 Jun 19.

Abstract

Motivation: A challenging problem after a genome-wide association study (GWAS) is to balance the statistical evidence of genotype-phenotype correlation with a priori evidence of biological relevance.

Results: We introduce a method for systematically prioritizing single nucleotide polymorphisms (SNPs) for further study after a GWAS. The method combines evidence across multiple domains including statistical evidence of genotype-phenotype correlation, known pathways in the pathologic development of disease, SNP/gene functional properties, comparative genomics, prior evidence of genetic linkage, and linkage disequilibrium. We apply this method to a GWAS of nicotine dependence, and use simulated data to test it on several commercial SNP microarrays.

Availability: A comprehensive database of biological prioritization scores for all known SNPs is available at http://zork.wustl.edu/gin. This can be used to prioritize nicotine dependence association studies through a straightforward mathematical formula-no special software is necessary.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Chromosome Mapping / methods*
  • DNA Mutational Analysis / methods*
  • Genetic Predisposition to Disease / genetics
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide / genetics*
  • Sequence Analysis, DNA / methods*
  • Tobacco Use Disorder / genetics*